People's day-to-day behavioral choices - including how to respond to stress and whether to be physically active - accumulate and compound to set their health risks and life expectancies. Indeed, two of every five premature deaths in the U.S. can be linked to unhealthy and ultimately modifiable behavioral choices. Despite good intentions to improve their health, people's attempts at midlife lifestyle change often fail, paving the way to late-life health limitations and costly chronic conditions. The overarching goal of the proposed research is to investigate how positive emotions alter biological systems in ways that ultimately reinforce sustained positive behavior change. An innovative upward spiral model of lifestyle change integrates the science of positive emotions with the emerging field of social genomics to describe pathways through which positive emotions may influence gene expression to undergird sustained behavior change. Specifically, we propose that positive emotions trigger peripheral biological changes that alter inflammation-related gene expression in ways that increasingly and implicitly reinforce wellness behaviors. Two studies - spanning laboratory and field - test this new model by targeting three Specific Aims. These aims are: (1) to identify peripheral biological resources and genetic polymorphisms that moderate the link between wellness behaviors and their positive emotion yield; (2) to identify the biological signaling pathways that mediate the proposed association between increases in positive emotions and changes in inflammation-related gene expression; and (3) to investigate the pathways through which increases in positive emotions influence changes in inflammation-related gene expression, sustained wellness behaviors, and associated health outcomes. Study 1 is a controlled laboratory study that investigates whether candidate peripheral biological resources (i.e., oxytocin, respiratory sinus arrhythmia, blood pressure, and C-reactive protein) and inflammation-related genetic polymorphisms moderate the positive emotion yield of wellness behaviors and thereby fuel upward spirals of healthy lifestyle change. Study 2 complements and extends this laboratory study, by testing the full scope of the upward spiral model of lifestyle change using a longitudinal, randomized, dual-blind, placebo-controlled field experiment with repeated measures of peripheral biological and genomic markers. This rigorous and validated longitudinal design is unprecedented in human social genomics research and can illuminate how wellness behaviors and biological health mutually reinforce one another. This program of translational research stands to forge a unified science of behavior change, reshape public health interventions, and unlock hidden opportunities to promote healthy longevity. PUBLIC HEALTH RELEVANCE: Unhealthy behavioral choices contribute to costly late life chronic diseases and premature death. Sustained positive behavior change is thus vital to promote healthy longevity, yet remains elusive. Understanding how positive emotions alter gene expression in ways that implicitly reinforce long-term adherence to positive health behaviors is needed to unlock evidence-based health interventions to promote health and save money and lives.